FC0082
Calmodulin  -  Myelin basic protein (MBP) 145-165

Biological function
Myelin basic protein (MBP) is a predominant protein in the multilamellar arrangement of the myelin sheath in the central nervous system. The myelin sheath has a dynamic structure that enables rapid signal propagation in the nervous system. This dynamic nature can be envisaged as the continuous formation and disruption of interactions in its protein content. Interactions of MBP can be modulated by with calcium(II) bound calmodulin (CaM).

Domain organization/sequence features
CaM is composed of two domains (the N-terminal and C-terminal domains), each of them being able to bind two calcium(II) ions. These domains can be considered rigid in the metal bound form (at least as far as the backbone is concerned), but they are quite free to move with respect to one another.

Structural evidence
MBP_145–165 affects the CaM protein conformational ensemble. CaM can adopt a large ensemble of conformations while in complex with the MBP_145–165. The structural heterogeneity revealed in the MBP_145–165-CaM complex could be a prerequisite for recognition pliability both for CaM and the MBP epitope. MOs of multiple conformations sampled by this complex were determined on the basis of simultaneous use of paramagnetic pcs and rdc restraints. The complex CaM-MBP_145–165 confers conformational heterogeneity, which differs from other CaM complexes.

Biochemical evidence
The binding site with the highest affinity to the MBP peptide is characterized by a dissociation constant (K_D) of 8.3 ± 0.1 μM, which is in good agreement with the one calculated from NMR spectroscopy. The affinities of the other two sites do not differ dramatically, being 11.8 ± 0.7 μM and 10.4 ± 0.1 μM. ITC measurements indicate three sets of binding sites, with the binding affinity being in the range 11.8 ± 0.7 μM to 8.3 ± 0.1 μM suggesting that the CaM-MBP_145–165 interaction might sample different conformations. MBP_{145– 165} affects the CaM protein conformational ensemble.

Mechanism category
tethering

Significance
The presence of heterogeneity, i.e. fuzziness in the MBP-calmodulin complexes provides the plasticity necessary to interact with a large number of different targets and enables the relevant recognition plasticity to take place.